Abstract

What is known and Objective: Long-acting intramuscular penicillin G injection is an important product for the management of some severe infections. However, testing the bioequivalence of such long-acting formulations is difficult. Our aim was to undertake such a test using a generic formulation containing 1 200 000 IU of benzathine penicillin G powder and an innovator's product (Retarpen (R) 1.2 million units; Sandoz, Switzerland). Methods: In an open, double-blind, randomized, two-periods, two-group crossover study, 12 healthy male volunteers received both formulations of benzathine penicillin G on two different days with a 5-month washout period between the doses and a sampling period of over 500 h. A simple, sensitive and rapid high-performance liquid chromatography (HPLC)-UV method was developed and validated for determination of penicillin G plasma concentrations and other pharmacokinetic (PK) parameters. Results and Discussion: The analytical method used produced linear responses within a wide analyte concentration range with average within-run and between-run variations of below 15% with acceptable recovery, accuracy and sensitivity. The primary PK parameters we used were maximum plasma concentration (C-max), time to reach the maximal concentration (T-max) and the area under the plasma concentration vs. time curve from time zero to the last sampling time (AUC(0 -> t)) using a standard non-compartmental approach. Based on these parameters, the two formulations were bioequivalent. What is new and Conclusion: We illustrate the bioequivalence testing of a very long-acting product. The data indicate that the generic test formulation and the branded reference formulation were bioequivalent in fasting healthy Iranian male volunteers.